AIDS and South Africa--towards a comprehensive strategy. Part II. Screening and control

In this, the second of a three-part series of articles in which we propose steps towards a comprehensive strategy for the control of HIV infection, we consider controversies relating to screening for HIV, the indications for and desirability of mandatory testing of certain groups at risk, and the place of voluntary testing in the control of HIV transmission and infection. Key recommendations are that mandatory testing of donors of blood and other vital tissues, patients on haemodialysis and haemodialysis unit staff is justified, and that children put up for adoption may require testing. We make further recommendations regarding HIV testing as a prerequisite for life insurance and recommend that voluntary testing be offered, supported by adequate pre- and post-test counselling. We consider that all health care workers should accept as their moral obligation the care and management of HIV-infected individuals, and that they should be adequately educated and skilled in such work. These recommendations were reached largely by consensus, although there were occasions when individual authors condoned recommendations with which they did not personally agree.     

Evaluation of a new generation of plastic evacuated blood-collection tubes in clinical chemistry, therapeutic drug monitoring, hormone and trace metal analysis.

Polyethylene terephthalate (PET) tubes have several advantages over glass tubes: they are unbreakable, lighter and more easily disposed of. Despite a steady increase in their use and an expansion of the range of available tubes, few studies validating their use have been published in the literature. This paper describes the various studies that have been performed to compare VENOJECT glass, VENOSAFE PET and VENOSAFE PET/heparin tubes for the assay of a panel of analytes in routine clinical chemistry, immunochemistry, hormone and tumor marker analysis and trace metal determination. These studies demonstrate that VENOSAFE PET tubes are a suitable alternative to glass tubes.     

Use of health care services for psychological distress by immigrants in an urban multicultural milieu.

OBJECTIVE: Research in the United States tends to attribute low rates of use of mental health services by immigrants to economic barriers. The purpose of our study was to examine this issue in the context of Canada's universal health care system. METHODS: A survey of the catchment area of a comprehensive clinic in Montreal interviewed random samples of 924 Canadian-born individuals and 776 immigrants born in the Caribbean (n = 264), Vietnam (n = 234), or the Philippines (n = 278) to assess their health care use for somatic symptoms, psychological distress, and recent life events. RESULTS: Overall rates of use of medical services in the past year were similar in immigrant (78.5%) and nonimmigrant (76.5%) groups. Rates of use of health care services for psychological distress were significantly lower among immigrants (5.5% compared with 14.7%, P < 0.001). This difference was attributable both to a lower rate of use of specialty mental health services by immigrants (2.5% compared with 11.7%, P < 0.001) and to differential use of medical services for psychological distress (3.5% compared with 5.8%, P = 0.02). When level of psychological distress was controlled, Vietnamese and Filipino immigrants were one-third as likely as Canadian-born residents to make use of mental health services. The lower rate of use by immigrants could not be explained by differences in sociodemographics, somatic or psychological symptoms, length of stay in Canada, or use of alternative sources of help. CONCLUSION: Immigrant status is associated with lower rates of use of mental health services, even with universal health insurance. This lower rate of use likely reflects cultural and linguistic barriers to care.     

Upregulation of CD40, CD80, CD83 or CD86 on alveolar macrophages after lung transplantation.

BACKGROUND: Alveolar macrophages (AMs) are known to be poor antigen-presenting cells, and lack the accessory molecules such as CD40, CD80 or CD86 to activate T cells. The question raised is about the potential changes in phenotypes after lung transplantation, particularly during acute rejection episodes. METHODS: The present study analyzed the phenotype of AMs longitudinally in 45 lung transplant patients, between August 1997 and April 2002, with a follow-up period of 27.2 +/- 2.5 (mean +/- SEM) months. There were 7.7 +/- 0.6 bronchoalveolar lavage (BAL) assessments performed per patient (i.e., 345 BALs), simultaneously with transbronchial biopsies. Transplantation was soon followed by a progressive upregulation of CD40 on 49.7 +/- 8% of AMs during the first month, and this marker remained elevated at 60 +/- 8% after 5 years. RESULTS: Both CD86 and CD80, as well as CD83, a marker of dendritic cells, were enhanced for most AMs during Grade A2 and A3 rejection episodes. A correlation was found between expression of CD83 and CD86, but not between CD1a and CD86. Immunohistology confirmed that CD40-positive cells in the alveoli corresponded to AMs and to some dendritic cells in the basal layers of the airways. In vitro studies showed that harvested AMs with these enhanced accessory molecules remained poor stimulators of allogeneic cells, a phenomenon that may be related to the ongoing immunosuppressive treatments. CONCLUSIONS: AM phenotypes showed marked changes during early or late acute rejection episodes, acquiring CD80, CD83 and CD86, while CD40 expression was further enhanced. This finding may provide clues on how to monitor the tolerance of transplanted lungs and may also provide new insights into the pathophysiology of lung transplantation.     

Interaction of the atypical neuroleptic clozapine with 5-HT3 receptors in the cerebral cortex and superior cervical ganglion of the rat

Clozapine, an atypical neuroleptic drug devoid of extrapyramidal side effects, was a moderately potent, competitive inhibitor of the binding of [3H]quaternised ICS 205-930 to 5-HT3 receptor sites in rat cortical membranes, possessing a pKi value of 7.0. In contrast, several other antipsychotic agents, including fluphenazine, alpha-flupenthixol, haloperidol, spiperone and (-)-sulpiride were essentially inactive. Clozapine also antagonised the 2-methyl 5-HT-induced depolarisation of the rat isolated superior cervical ganglion, a response known to be mediated via 5-HT3 receptors. Clozapine (0.1-1 microM) induced parallel displacements to the right of the dose-response curve to 2-methyl 5-HT in this tissue, possessing a pKb value of 7.3. These data suggest that the atypical antipsychotic profile of clozapine may be related, at least, in part to its ability to interact with central 5-HT3 receptor sites.     

A respiratory survey in a black Johannesburg workforce.

BACKGROUND--The burden and determinants of airway disease in the population of southern Africa, which is currently undergoing rapid, often uncontrolled, urbanisation and industrialisation, are unknown. Previous surveys have focused on specific occupational groups and few have included women. This paper describes the respiratory status in a 30% probability sample of 206 men and 203 women drawn from an urban black Johannesburg workforce of almost 1500, all working for an educational institution. METHODS--Subjects answered a respiratory questionnaire and performed spirometric tests. Symptom rates and age and height standardised forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC%, and forced expiratory flow (FEF25-75) were analysed by gender in relation to smoking, past work exposures, past and recent respiratory conditions, and socioeconomic indicators. RESULTS--Symptom prevalence was high, bronchitic symptoms in men being related to smoking and previous occupational exposure, and in women to smoking despite the low intensity of their habit. Phlegm and wheezing were related to childhood respiratory illness in both men and women. FVC and FEV1, based on all subjects including smokers, were higher than previously reported for black residents of southern Africa. FVC was also positively related to education and job category. Higher values for ever smokers than for never smokers suggested health selection into the habit, while significant negative smoking effects were seen only on FEV1/FVC% and only in women. CONCLUSIONS--Despite the high prevalence of symptoms--some smoking related--in this urban workforce, lung function levels were higher than previously reported in African blacks, and may reflect improving socioeconomic conditions.     

A multicentre double-blind comparison of hydroxyzine, buspirone and placebo in patients with generalized anxiety disorder

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14,12,28 and 35. Seventy percent of the patients were female; the average age was 41 ± 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 ± 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD. Received: 26 January 1998/Final version: 15 May 1998     

Cranial sutures and craniometric points detected on MRI

The main goal of the study was to determine on MRI the cranial sutures, the craniometric points and craniometric measurements, and to correlate these results with classical anthropometric measurements. For this purpose, we reviewed 150 cerebral MRI examinations considered as normal (Caucasian population aged 2049 years). For each examination we individualized 11 craniometric landmarks (Glabella, Bregma, Lambda, Opisthocranion, Opisthion, Basion, Inion, Porion, Infra-orbital, Eurion) and three measurements. Measurements were also calculated independently on 498 dry crania (Microscribe 3-DX digitizer). To validate the MRI procedure, we measured four dry crania by MRI and with compass or digital caliper gauges. Cranial sutures always appeared without signal (black), whatever the MRI sequence used, and they are better visualized with a 5 mm slice thickness (compact bone overlapping). Slice dynamic analysis and multiplanar reformatting allowed the detection of all craniometric points, some of these being more difficult to detect than others (Porion, Infra-orbital). The measurements determined by these points were as follows: VertexBasion height=135.66±6.56 mm; EurionEurion width=141.17±5.19 mm; GlabellaOpisthocranion length=181.94±6.40 mm. On the midline T1-weighted sagittal image, all median craniometric landmarks can be individualized and the GlabellaOpisthocranion length, VertexBasion height and parenchyma indices can be calculated. Craniometric points and measurements between these points can be estimated with a standard cerebral MRI examination, with results that are similar to anthropometric data.     

Early Impairment of CD8+ T Cells Immune Response Against Epstein–Barr Virus (EBV) Antigens Associated with High Level of Circulating Mononuclear EBV DNA Load in HIV Infection

Immunodeficiency related to HIV may increase the incidence of EBV-associated lymphomas, by altering EBV-specific immune control and consequently favoring EBV reactivation. The aim of the present study was to assess the relationship between the decrease of EBV-specific cellular immunity and the increase of EBV reactivation in a prospective cohort of 72 unselected HIV-infected individuals. EBV-specific immunity was evaluated by a highly sensitive IFN-gamma ELISPOT assay using 22 peptides mimicking latent and lytic antigens, and circulating mononuclear (PBMC) EBV DNA load was quantified by real-time quantitative PCR. The mean circulating cell-associated EBV DNA load was higher in HIV-infected patients (639 copies/10(6) PBMC) than in healthy controls (21, n = 14) ( P = 0.005) and was higher in patients with CD4(+) T-cell count below 350/microL than that in patients harboring higher CD4(+) T-cell count (1112 vs. 389, P = 0.003). The mean intensity of EBV-specific cellular responses was lower in HIV-infected patients than in controls ( P = 0.001), even in patients with CD4(+) T-cell count above 350/-microL ( P = 0.007). The number of EBV peptides recognized was lower in HIV-infected patients than in controls (frequency: 0.44 vs. 0.67; P = 0.02), indicating reduced polyclonality in HIV-infected patients. The polyclonality was 1.5-fold lower in HIV-infected patients with CD4(+) T-cell count below 350/-microL ( P =0.007). For EBV load >1000 copies/10(6) PBMC, the levels of cell-associated EBV DNA and those of EBV-specific cellular immunity, either in intensity or in polyclonality, or both, were inversely correlated. These findings demonstrate early impairment of the EBV-specific cellular immune control with progressive increase of EBV reactivation in the course of HIV infection. These observations likely provide a basis for appreciating the risk to develop non-Hodgkin's lymphomas in HIV-infected individuals.     

Antifungal coating by biofunctionalized polyelectrolyte multilayered films

The surface of medical devices is a common site of bacterial and fungal adhesion, first step to the constitution of a resistant biofilm leading frequently to chronic infections. In order to prevent such complications, several physical and chemical modifications of the device surface have been proposed. Here, we experiment a new type of topical antifungal coating using the layer-by-layer technique. The nanometric multilayer film obtained by this technique is functionalized by the insertion of a chromogranin A-derived antifungal peptide (CGA 47-66, chromofungin). We show that the embedded peptide keeps its antifungal activity by interacting with the fungal membrane and penetrating into the cell. In vitro studies demonstrate that such an antifungal coating is able to inhibit the growth of yeast Candida albicans by 65% and completely stop the proliferation of filamentous fungus Neurospora crassa. The cytotoxicity of such a coating was also assessed by growing human gingival fibroblasts at its surface. Finally, the antifungal coating of poly(methylmethacrylate), a widely used material for biomedical devices, is successfully tested in an in vivo oral candidiasis rat model. Taken together, these results assessed the functionalized multilayer films containing a new potent antifungal non-toxic peptide, as a novel and promising technique for local antifungal protection.